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Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies

Lee JH; Budanov AV; Bodmer R; Bier E; Karin M et al. · 2010 · Science · Atlas ID LEE2010

What this study shows

The one study that connects an amino-acid sensor to an organismal ageing phenotype. Loss of Drosophila Sestrin produced triglyceride accumulation, mitochondrial dysfunction, muscle degeneration and cardiac malfunction - all prevented by inhibiting TOR or activating AMPK. Sestrin sits in a negative feedback loop: TOR activity drives Sestrin expression, and Sestrin inhibits TOR back.

Tier C because it is an animal intervention or observation study measuring an organismal outcome (model: Drosophila melanogaster (dSesn loss-of-function)); tier describes study design, not quality -- animal evidence can be rigorous and still sit below direct human data.

At a glance

Evidence tier	C Animal in vivo
Study type	4 - Animal Study
Model system	Drosophila melanogaster (dSesn loss-of-function)
Journal	Science
Year	2010
Peer reviewed	Yes
Record last updated	2026-07-29
Source	DOI 10.1126/science.1182228 · PMID 20203043

Extracted findings

Intervention	dSesn loss of function; rapamycin; AMPK activation
Target	Sestrin -> AMPK/TOR feedback loop
Model	Drosophila
Effect	Sestrin loss causes age-related muscle, cardiac and metabolic pathology in flies; rescued by TOR inhibition or AMPK activation

In the Atlas

Open questions that cite this study

Cited as supporting evidence for the open question Sensor-selective geroprotection without the metabolic penalty.

Abstract

Sestrins are conserved proteins that accumulate in cells exposed to stress, potentiate adenosine monophosphate-activated protein kinase (AMPK), and inhibit activation of target of rapamycin (TOR). We show that the abundance of Drosophila sestrin (dSesn) is increased upon chronic TOR activation through accumulation of reactive oxygen species that cause activation of c-Jun amino-terminal kinase and transcription factor Forkhead box O (FoxO). Read the full abstract on PubMed →

Cite this record

Barton, O. (2026). Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies — evidence-graded record LEE2010. In Oliver's mTOR Atlas. https://mtor-atlas.org/study/LEE2010/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_LEE2010,
  author       = {Barton, Oliver},
  title        = {{Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies} --- evidence-graded record LEE2010},
  howpublished = {Oliver's mTOR Atlas},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/LEE2010/},
  note         = {Dataset DOI: 10.5281/zenodo.22059963}
}

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